Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis.
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ABSTRACT:
SUBMITTER: Jiang S
PROVIDER: S-EPMC11236318 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
Publications
Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis.
Jiang Shengpan S Zhu Guoting G Tan Yiqing Y Zhou Tao T Zheng Shilin S Wang Fuhua F Lei Wenfeng W Liu Xuan X Du Jinjun J Tian Manman M
Aging 20240613 12
Microangiogenesis is an important prognostic factor in various cancers, including hepatocellular carcinoma (HCC). The Vascular Endothelial Growth Factor (VEGF) has been shown to contribute to tumor angiogenesis. Recently, several studies have investigated the regulation of VEGF production by a single gene, with few researchers exploring all genes that affect VEGF production. In this study, we comprehensively analyzed all genes affecting VEGF production in HCC and developed a risk model and gene- ...[more]
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Project description:BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis.MethodsmRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines.ResultsFive GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples.ConclusionsWe identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.
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Project description:Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. Epigenetic dysregulation is now considered to be related to hepatocarcinogenesis. However, it is unclear how epigenetic-related genes (ERGs) contribute to the prognosis of HCC. In this study, we used the TCGA database to identify prognostic ERGs that were differentially expressed in HCC patients. Then, using least absolute shrinkage and selection operator (LASSO) regression analysis, a six-gene signature was constructed, and patients were divided into high- and low-risk groups. Validation was performed on HCC patients from the ICGC database. Patients in the high-risk group had a significantly lower chance of survival than those in the low-risk group (p < 0.001 in both databases). The predictive ability of the signature was determined by the receiver operating characteristic (ROC) curve. The risk score was then shown to be an independent prognostic factor for the overall survival (OS) of HCC patients based on the results of univariate and multivariate analyses. We also created a practical nomogram combining the prognostic model with other clinical features. Moreover, functional enrichment analysis revealed that these genes are linked to tumor immunity. In conclusion, our findings showed that a novel six-gene signature related to epigenetics can accurately predict the occurrence and prognosis of HCC.
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Project description:Metabolic reprogramming is one of the crucial hallmarks of cancer. Hepatocellular carcinoma (HCC) resulting from hepatitis B has various altered metabolic features. However, the impact of such alterations on the tumor microenvironment (TME) and immunotherapy efficacy is still unclear. Here, a prognostic signature of metabolism-related gene (MRG) composition was constructed, and the immune profile of different subgroups and potential response to immunotherapy were described. Based on the HCC gene dataset, we used weighted gene coexpression network analysis for identifying MRGs linked to hepatitis B. An MRG prognostic index (MRGPI) with two genes, ATIC and KIF2C, was constructed using Cox regression analysis, an independent prognostic factor. In addition, the model was validated using the GEO dataset. The immune profile and prediction of HCC response to immunotherapy in different subgroups were analyzed using CIBERSORT and TIDE. Based on the outcomes, the distributions of memory B cells, monocytes, resting mast cells, and M0 macrophages in TME were different with a greater benefit of immunotherapy in the low MRGPI risk group. In addition, the MRGPI risk groups showed substantial differences in sensitivity to conventional drug therapy. This study concludes that MRGPI is an effective biomarker for predicting the prognoses of patients with HCC resulting from hepatitis B virus infections and determining the efficacy of immunotherapy and conventional medical therapy.
| S-EPMC9441393 | biostudies-literature
Project description:BackgroundTumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients.MethodsGene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments.ResultsAn EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion.ConclusionThe EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.
| S-EPMC7953549 | biostudies-literature